DOCSLIB.ORG

RT-LAMP Has High Accuracy for Detecting SARS-Cov-2 in Saliva and 2 Naso/Oropharyngeal Swabs from Asymptomatic and Symptomatic Individuals

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
RT-LAMP Has High Accuracy for Detecting SARS-Cov-2 in Saliva and 2 Naso/Oropharyngeal Swabs from Asymptomatic and Symptomatic Individuals medRxiv preprint doi: https://doi.org/10.1101/2021.06.28.21259398; this version posted August 20, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 1 RT-LAMP has high accuracy for detecting SARS-CoV-2 in saliva and 2 naso/oropharyngeal swabs from asymptomatic and symptomatic individuals 3 Short title: RT-LAMP for detecting SARS-CoV-2 in saliva and naso/oropharyngeal swabs 4 †Stephen P. Kidd1,2, †Daniel Burns1,3, Bryony Armson1,2,4, Andrew D. Beggs5, Emma L. A. Howson6, 5 Anthony Williams7, Gemma Snell7, Emma L. Wise1,8, Alice Goring1, Zoe Vincent-Mistiaen9, Seden 6 Grippon1, Jason Sawyer10, Claire Cassar10, David Cross10, Tom Lewis10, Scott M. Reid10, Samantha 7 Rivers10, Joe James10, Paul Skinner10, Ashley Banyard10, Kerrie Davies11, Anetta Ptasinska5, Celina 8 Whalley5, Jack Ferguson5, Claire Bryer5, Charlie Poxon5, Andrew Bosworth5, Michael Kidd5,12, Alex 9 Richter13, Jane Burton14, Hannah Love14, Sarah Fouch1, Claire Tillyer1, Amy Sowood1, Helen Patrick1, 10 Nathan Moore1, Michael Andreou15, Nick Morant16, Rebecca Houghton1, Joe Parker17, Joanne Slater- 11 Jefferies17, Ian Brown10, Cosima Gretton2, Zandra Deans2, Deborah Porter2, Nicholas J. Cortes1,9, Angela 12 Douglas2, Sue L. Hill2, *Keith M. Godfrey18,19, +Veronica L. Fowler1,2 13 14 1Hampshire Hospitals NHS Foundation Trust, Department of Microbiology, Basingstoke and North Hants 15 Hospital, Basingstoke, UK 16 2NHS Test and Trace Programme, Department of Health and Social Care, UK 17 3School of Electronics and Computer Science, University of Southampton, UK 18 4vHive, School of Veterinary Medicine, University of Surrey, Guildford, UK 19 5University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK 20 6The Pirbright Institute, Ash Road, Pirbright, Woking, UK 21 7University of Southampton & Division of Specialist Medicine, University Hospital Southampton, UK 22 8School of Biosciences and Medicine, University of Surrey, Guildford, UK 23 9Gibraltar Health Authority, Gibraltar, UK 24 10Animal and Plant Health Agency, New Haw, Addlestone, Surrey, UK 25 11Leeds Teaching Hospitals NHS Trust and University of Leeds, UK 26 12Public Health West Midlands Laboratory, Birmingham, UK 27 13Institute of Immunology and Immunotherapy, University of Birmingham, UK 28 14High Containment Microbiology, National Infection Service, Public Health England, Porton Down, UK 29 15OptiSense Limited, Horsham, West Sussex, UK 30 16GeneSys Biotech Limited, Camberley, Surrey, UK 31 17National Biofilms Innovation Centre, University of Southampton, UK 32 18NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital, UK 33 19MRC Lifecourse Epidemiology Centre, University of Southampton, UK 34 35 †Denotes co-first authorship; +Senior author; *Corresponding author: - [email protected]; 36 NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. Page 1 of 43 medRxiv preprint doi: https://doi.org/10.1101/2021.06.28.21259398; this version posted August 20, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 37 Abstract 38 Previous studies have described RT-LAMP methodology for the rapid detection of SARS-CoV-2 in 39 nasopharyngeal/oropharyngeal swab and saliva samples. Here we describe the validation of an 40 improved sample preparation method for extraction free Direct RT-LAMP and define the clinical 41 performance of four different RT-LAMP assay formats for detection of SARS-CoV-2 within a large-scale 42 multisite clinical evaluation. 43 We describe Direct RT-LAMP on 559 swabs and 86,760 saliva samples and RNA RT-LAMP on extracted 44 RNA from 12,619 swabs and 12,521 saliva samples collected from asymptomatic and symptomatic 45 individuals across multiple healthcare and community settings. 46 For Direct RT-LAMP, we found a diagnostic sensitivity (DSe) of 70.35% (95% CI 63.48-76.60%) on swabs 47 and 84.62% (79.50-88.88%) on saliva, with diagnostic specificity (DSp) of 100% (98.98-100.00%) on 48 swabs and 100% (99.72-100.00%) on saliva when compared to RT-qPCR. Analysing samples with RT- 49 qPCR ORF1ab CT values of <25 and <33 (high and medium-high viral copy number, respectively), we 50 found DSe of 100% (96.34-100%) and 77.78% (70.99-83.62%) for swabs, and 99.01% (94.61-99.97%) 51 and 87.32% (80.71-92.31%) for saliva. For RNA RT-LAMP DSe and DSp were 95.98% (92.74-98.06%) 52 and 99.99% (99.95-100%) for swabs, and 80.65% (73.54-86.54%) and 99.99% (99.95-100%) for saliva, 53 respectively. 54 The findings from these evaluations demonstrate that RT-LAMP testing of swabs and saliva is 55 applicable to a variety of different use-cases, including frequent, interval-based testing of saliva from 56 asymptomatic individuals via Direct RT-LAMP that may otherwise be missed using symptomatic testing 57 alone. 58 59 60 Page 2 of 43 medRxiv preprint doi: https://doi.org/10.1101/2021.06.28.21259398; this version posted August 20, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 61 Author Summary 62 Rapid diagnostic testing at scale to identify and isolate symptomatic and asymptomatic individuals 63 potentially transmitting infectious SARS-CoV-2 is an essential part of the response to the COVID-19 64 pandemic. RT-LAMP on both extracted RNA and directly on crude samples potentially provides faster 65 turnaround times than reverse-transcriptase quantitative real-time PCR testing, with a higher 66 sensitivity and specificity than antigen lateral flow devices. Increasing evidence points to potential 67 benefits of SARS-CoV-2 testing using saliva rather than nasopharyngeal/oropharyngeal swabs, leading 68 us to undertake a multi-site evaluation of an improved simple sample preparation method for Direct 69 SARS-CoV-2 RT-LAMP. Our study demonstrated that the RNA RT-LAMP assay has high sensitivity and 70 specificity, providing a rapid alternative to RT-qPCR testing with a reliance on differing reagents and 71 equipment. The simple SARS-CoV-2 Direct RT-LAMP preparation method also demonstrated high 72 sensitivity and specificity for detecting SARS-CoV-2 in saliva and naso/oropharyngeal swabs from 73 asymptomatic and symptomatic individuals, notably in saliva samples from which the individual would 74 likely be considered infectious. The findings highlight the usefulness of saliva as a simple to collect, 75 non-invasive, sample type, potentially applicable for interval-based testing of asymptomatic 76 individuals. 77 Page 3 of 43 medRxiv preprint doi: https://doi.org/10.1101/2021.06.28.21259398; this version posted August 20, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 78 Introduction 79 Rapid diagnostic testing to identify and isolate symptomatic and asymptomatic individuals 80 potentially transmitting infectious viral pathogens is an essential requirement of any pandemic 81 response. The novel betacoronavirus, SARS-CoV-2, initially identified after an outbreak of viral 82 pneumonia in Wuhan, China in December 2019(1), has rapidly spread throughout the world, causing 83 over 141 million confirmed cases and over 3.1 million deaths(2), (April, 2021). 84 Conventional diagnostics for SARS-CoV-2 consist of RNA enrichment followed by reverse- 85 transcriptase quantitative real-time PCR (RT-qPCR) against one or more viral gene targets(3). 86 However, this methodology requires sample inactivation, RNA extraction and RT-qPCR thermal 87 cycling, meaning that the time from sample-to-result can often be several hours, and requires 88 centralised equipment and personnel trained in Good Laboratory Practice to perform testing. 89 We have previously shown the utility of reverse-transcriptase loop mediated isothermal 90 amplification (RT-LAMP) for the detection of SARS-CoV-2 both from extracted RNA (RNA RT-LAMP) 91 and directly from nasopharyngeal/oropharyngeal swabs (Direct RT-LAMP)(4). RT-LAMP utilises a 92 rapid and stable DNA polymerase that amplifies target nucleic acids at a constant temperature. This 93 removes the requirement for conventional thermal cycling allowing RT-LAMP reactions to be 94 performed in shorter reaction times using less sophisticated platforms. 95 In a study of 196 clinical samples(4), testing of RNA extracted from nasopharyngeal/oropharyngeal 96 swabs collected into viral transport media (VTM) using RNA RT-LAMP demonstrated a diagnostic 97 sensitivity (DSe) of 97% and a diagnostic specificity (DSp) of 99% in comparison to RT-qPCR of the 98 ORF1ab region of SARS-CoV-2. For Direct RT-LAMP on crude swab samples, the DSe and DSp were 99 67% and 97%, respectively. When a cycle threshold (CT) cut-off for RT-qPCR of < 25 was considered, 100 reflecting the increased likelihood of detecting viral RNA from active viral replication, the DSe of 101 Direct RT-LAMP increased to 100% (4). Page 4 of 43 medRxiv preprint doi: https://doi.org/10.1101/2021.06.28.21259398; this version posted August 20, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
Load more

Recommended publications
  • Heterogeneous Supercomputer Advances Viral Research and Animal Health
    Heterogeneous Supercomputer Advances Viral Research and Animal Health Atos supercomputer with Intel® processors helps the Pirbright Institute safeguard livestock and humans from the rising threat of viral diseases The Context The Challenge The Solution When a deadly virus emerges, scientists • Rising demand for computational Taking advantage of Intel® technologies must respond rapidly to characterize resources threatened to outstrip and Atos expertise, Pirbright implemented the virus, track its spread, and stop it from the capacity provided by Pirbright’s legacy an Atos HPC system with heterogeneous devastating livestock and possibly infecting mix of servers, clusters, and workstations. nodes based on the Intel® Xeon® processor humans. As a global leader in this work, • Pirbright sought a versatile system E7 and E5 families. the Pirbright Institute in the UK needs that could accelerate progress in areas flexible high-performance computing (HPC) such as genome assembly of complex Atos Life Sciences Center of Excellence resources that can handle a wide variety viruses and hosts, epidemiology studies (LSCoE) experts worked hand in hand of workloads. Pirbright deployed an Atos to monitor virus migration, with Pirbright to provide a bespoke compute supercomputer powered by Intel® Xeon® and the development of innovative platform to enable researchers increase processors. With a unified environment analytics tools. the efficiency of their processes and running its diverse applications, Pirbright ultimately ensure the control of viral diseases. enhances scientific productivity and helps policymakers respond effectively when a viral outbreak threatens. Located in Surrey, England, Pirbright is the UK’s flagship research center focused The results • ·By running its diverse workloads on giving the UK capabilities on a unified environment, Pirbright lowers to predict, detect, understand, and respond management overhead and avoids to economically important viral diseases the time and expense of moving vast of livestock.
    [Show full text]
  • Reader/Professor of Vaccinology
    READER/PROFESSOR OF VACCINOLOGY AT THE UNIVERSITY OF SURREY IN COLLABORATION WITH THE PIRBRIGHT INSTITUTE RECRUITMENT INFORMATION PACK BUILDING BRILLIANCE AT SURREY, EVERY STEP COUNTS, EVERY LITTLE DISCOVERY. The Faculty of Health and Medical Sciences has research partners in over 40 different countries worldwide. The Faculty offers an extensive portfolio of teaching programmes with considerable league table success for undergraduate, postgraduate, research and continuing professional development courses. Ranked 1st for Food Science, 1st for Veterinary Medicine, 5th for Psychology and 7th for Biosciences in the UK, the Faculty offers courses that are academically rigorous and practically relevant. The Faculty is ranked top ten for research in the UK. (REF 2014), 93 per cent of our biosciences, health, psychology and veterinary research was rated world-leading or internationally excellent, placing Surrey eighth out of 94 institutions in the Allied Health category. 02 ENTER A WORLD OF COLLABORATION SURREY IS MADE UP OF MANY TALENTED INDIVIDUALS WHO MAKE US A GREAT INSTITUTION. AND WORKING TOGETHER, AND CONNECTING WITH EXTERNAL INSTITUTIONS, BUSINESSES AND GOVERNMENT MAKE US EVEN STRONGER. Since the University’s founding in the 1960s, and technologies that will drive the UK’s future economic before that at Battersea College, our community growth. We also saw the first successful deployment of has thrived on strong connections with the world the RemoveDEBRIS satellite, a project we are leading outside our campus. This spirit of collaboration is with a consortium of space sector organisations. evident across the University today at every level. There’s real energy, momentum and ambition It informs our teaching, adds value to our research to Surrey.
    [Show full text]
  • Bovine Pestivirus Heterogeneity and Its Potential Impact on Vaccination and Diagnosis
    viruses Review Bovine Pestivirus Heterogeneity and Its Potential Impact on Vaccination and Diagnosis 1, 1 2 3,4 Victor Riitho y , Rebecca Strong , Magdalena Larska , Simon P. Graham and Falko Steinbach 1,4,* 1 Virology Department, Animal and Plant Health Agency, APHA-Weybridge, Woodham Lane, New Haw, Addlestone KT15 3NB, UK; [email protected] (V.R.); [email protected] (R.S.) 2 Department of Virology, National Veterinary Research Institute, Al. Partyzantów 57, 24-100 Puławy, Poland; [email protected] 3 The Pirbright Institute, Ash Road, Pirbright GU24 0NF, UK; [email protected] 4 School of Veterinary Medicine, University of Surrey, Guilford GU2 7XH, UK * Correspondence: [email protected] Current Address: Centre of Genomics and Child Health, The Blizard Institute, Queen Mary University of y London, London E1 2AT, UK. Received: 4 September 2020; Accepted: 3 October 2020; Published: 6 October 2020 Abstract: Bovine Pestiviruses A and B, formerly known as bovine viral diarrhoea viruses (BVDV)-1 and 2, respectively, are important pathogens of cattle worldwide, responsible for significant economic losses. Bovine viral diarrhoea control programmes are in effect in several high-income countries but less so in low- and middle-income countries where bovine pestiviruses are not considered in disease control programmes. However, bovine pestiviruses are genetically and antigenically diverse, which affects the efficiency of the control programmes. The emergence of atypical ruminant pestiviruses (Pestivirus H or BVDV-3) from various parts of the world and the detection of Pestivirus D (border disease virus) in cattle highlights the challenge that pestiviruses continue to pose to control measures including the development of vaccines with improved cross-protective potential and enhanced diagnostics.
    [Show full text]
  • Download the Guildford Local Plan
    Schedule of proposed main modifications to the Submission Local Plan (2017) The proposed main modifications to the Submission Local Plan: Strategy and Sites are set out below. Text added is shown as underlined and deleted text is shown as strikethrough. Where maps have been modified, the area of change is shown within a yellow box and additions and deletions are shown on small inset maps. Contents Policies 2 Sites 46 Appendices 61 Appendix 1: Housing Trajectory 64 Appendix 2: Maps 67 1 Policies Mod Paragraph Proposed Modification No. or Section Policy S1: Presumption in favour of sustainable development MM1 Policy para (3) Where there are no policies relevant to the application or relevant policies are out of date at the time of (3)(a) making the decision, then the Council will grant permission unless material considerations indicate otherwise, taking into account whether: a) Specific policies in that Framework indicate that development should be restricted.The application of policies in the National Planning Policy Framework that protect areas or assets of particular importance provides a clear reason for refusing the development proposed; or MM1 Reasoned 4.1.4 Local Planning Authorities are encouraged to include a policy within their Local Plan that embraces the Justification presumption in favour of sustainable development. Policy S1 meets this requirement and adopts the para 4.1.4 model wording suggested. When implementing Policy S1, local circumstances will be taken into account to respond to different opportunities for achieving
    [Show full text]
  • 16Th International Veterinary Biosafety Workgroup Meeting Delegate
    16th International Veterinary Biosafety Workgroup Meeting Hosted by The Pirbright Institute, UK 10 – 12 June 2014 Delegate Information Pack Final Information 16th International Veterinary Biosafety Workgroup Hosted by The Pirbright Institute, UK 10 – 12 June 2014 Contents 1. Outline programme ………………………………………………………… 1 2. Meeting venues and security……………………………………………… 1 3. Accommodation ……………………………………………………………. 2 4. Travel ……………………………………………………………………….. 3 5. Provided transport ………………………………………………………… 4 6. Registration ……………………………………………………………….... 5 7. Tours, Social events and meals ………..………………………………... 5 8. Instructions for presenters ………………………………………………… 5 9. Local information …………………………………………………………... 5 1. Outline programme Date Programme Location 9 June 14:00 – 17:00 Duty Holder Meeting The Pirbright Institute, (Closed meeting) Pirbright. GU24 0NF 10 June 16th International Veterinary Biosafety Workgroup Meeting H.G. Wells Conference (day one) Centre, Woking. GU21 6HJ Please see below regarding road closures. 11 June 16th International Veterinary Biosafety Workgroup Meeting AHVLA, New Haw. (day two) KT15 3NB 12 June 16th International Veterinary Biosafety Workgroup Meeting Public Health England, (day three) Porton Down, SP4 0JG 13 June EU FMD Safety Officers Meeting TBC 2. Meeting venues and security The meeting will take place at several venues over the three days of the 16th International Veterinary Biosafety Workshop Meeting. Please remember to keep photo ID on you as this will be required for accessing secure sites. The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey. GU24 0NF Directions: http://www.pirbright.ac.uk/About/ContactUs.aspx Please be aware if visiting the Institute, for the closed meeting or as part of the tour group, you will be required to sign in with security and show photo id before entering the site. Biosecurity restrictions also apply to some areas.
    [Show full text]
  • Pirbright Institute - Wikipedia Pirbright Institute
    1/29/2020 Pirbright Institute - Wikipedia Pirbright Institute The Pirbright Institute (formerly the Institute for Animal The Pirbright Institute Health) is a research institute in Surrey, England, dedicated to (Previously: Institute for the study of infectious diseases of farm animals. It forms part of Animal Health) the UK government's Biotechnology and Biological Sciences Research Council (BBSRC). The Institute employs scientists, vets, Abbreviation N/A PhD students and operations staff. Formation 1987 Legal status Government-funded research institute Contents (registered charity) Purpose Farm animal health History and diseases in the Directors of note UK Structure Location Ash Road, Pirbright, Funding Surrey, England Function Region UK Location served See also Membership Around 350 staff - half researchers, References half operations External links Director Dr Bryan Charleston Parent BBSRC History organization Affiliations DEFRA It began in 1914 to test cows for tuberculosis. More buildings were Budget c.£30m added in 1925. Compton was established by the Agricultural Website [1] (http://www.pirbri Research Council in 1937. Pirbright became a research institute in ght.ac.uk) 1939 and Compton in 1942. The Houghton Poultry Research Station at Houghton, Cambridgeshire was established in 1948. In 1963 Pirbright became the Animal Virus Research Institute and Compton became the Institute for Research on Animal Diseases. The Neuropathogenesis Unit (NPU) was established in Edinburgh in 1981. This became part of the Roslin Institute in 2007. In 1987, Compton, Houghton and Pirbright became the Institute for Animal Health, being funded by BBSRC. Houghton closed in 1992, operations at Compton are being rapidly wound down with the site due to close in 2015.
    [Show full text]
  • Corporate Report 2019 the Pirbright Institute Annual Report 2019 Director’S Welcome
    PREVENTING AND CONTROLLING VIRAL DISEASES CORPORATE REPORT 2019 THE PIRBRIGHT INSTITUTE ANNUAL REPORT 2019 DIRECTOR’S WELCOME Cover image: © Professor Bryan Charleston, Director’s Welcome 3 Director A VISION About Pirbright 6 African buffalo (Syncerus caffer) FOR HEALTH are the primary carrier host of Our Expertise 8 foot-and-mouth disease virus (FMDV) in African savannah Scientific Impact 10 ecosystems, where the disease is endemic. The cover image A Global Centre of Excellence 15 shows one of the captured buffalo housed in the veterinary facilities in Skukuza, Kruger Science for Everyone 16 National Park, South Africa. The studies showed some viruses Investment in the Future 18 persist for up to 400 days in buffaloes Working with Industry 21 Global Collaborations 22 Our Success Stories 26 Emerging diseases, particularly viruses that Pirbright is one of the few laboratories in and Zika – as well as carrying out research Developing Our Culture have the potential to cause pandemics in the world that has continued research on their livestock hosts and insect vectors. and Workforce 28 animals and humans, are a growing concern, into ASF over the past 20 years and we are All have epidemic potential and insufficient World Class Expertise 29 and international disease control agencies currently working to develop a vaccine as control measures, and our research will quite rightly recognise the need for funding well as testing antivirals for this devastating support the drive to be ready to respond. Pirbright Performance 29 in scientific research
    [Show full text]
  • Training the Veterinary Professionals of the Future University of Surrey
    UNIVERSITY OF SURREY SCHOOL OF VETERINARY MEDICINE Guildford, Surrey GU2 7XH, UK T: +44 (0) 1483 689 165 E: [email protected] surrey.ac.uk/vet TRAINING THE VETERINARY PROFESSIONALS OF THE FUTURE Every effort has been made to ensure the accuracy of the information contained in this publication at the time of going to press. 6313-1113 The University reserves the right, however, to introduce changes to the information given. November 2013 The University of Surrey School of Veterinary Medicine CONTENTS We are delighted to have risen to 8th position in the Guardian University Guide 2014, up from 12th position last year. We also climbed 14 places to 12th position in the Times/Sunday Times Good University Guide, nine places to 13th in the Complete University Guide 2014 and are now rated number two in Over 1000 partner organisations work with us to the South East, second only to Oxford University provide students from all parts of the University with 2 in both tables. vital experience of the professional environment. Welcome .................................................. 2 * Introduction ........................................... 4 Our School ............................................... 6 Our Programmes .................................. 8 The results of the latest National Student Survey Our Staff ................................................. 10 (NSS) revealed that our students are happier with Our Partners ����������������������������������������� 12 their studies at Surrey than ever before. A record-breaking 92 per cent* of respondents Research Case Studies ..................... 16 expressed their satisfaction with the overall quality Work With Us ...................................... 20 of their higher education, a rise of two per cent from 2012. The result helped us climb to ninth in the overall NSS table.
    [Show full text]
  • List of Institutions and Laboratories
    APPROVED INSTITUTIONS AND LABORATORIES FOR PARTICIPATION UNDER THE PUBLIC RESEARCH INSTITUTIONS (PRI) AND INDUSTRIAL RESEARCH LABORATORIES (IRL) SCHEMES. UNITED KINGDOM SITES Bayer UK Ltd National Environmental Technology Cancer Research UK Centre, Oxfordshire Centre for Cancer Treatment, Mount National Institute for Biological Standards Vernon Hospital Control Central Veterinary Laboratory Natural History Museum, London Defence Science and Technology NERC Institute of Virology & Laboratory, Porton Down Environmental Microbiology, Oxford Department for Environmental, Food and Nuffield Institute of Comparative Medicine Rural Affairs Pfizer UK Ltd GlaxoSmithKline Ltd Public Health Laboratory, St Luke’s Health Protection Agency Hospital, Guildford, Surrey Institute of Arable Crops Research Pirbright Institute Institute for Clinical Research, Roche Products Ltd Maidenhead Royal Botanic Gardens, Kew Lilly Research Centre Royal Institution of Great Britain Marie Curie Research Foundation Sanger Institute, Cambridge Marie Curie Research Institute Science Museum, London Merck Sharp and Dohme Unilever Research Laboratory MRC Clinical Research Centre, Northwick Water Research Centre - Marlow, Slough Park Hospital and Swindon MRC Clinical Trials Unit, Euston Road, Wellcome Institute of Comparative London Physiology, London Zoo MRC Laboratories, Carshalton Wyeth Institute of Medical Research MRC Molecular Neurobiology Unit Zoological Society of London MRC National Institute for Medical Research MRC Rheumatism Research Institute, Taplow INTERNATIONAL SITES MRC Gambia MRC Jamaica MRC Uganda World Health Organisation, Department of Reproductive Health Research, Geneva, Switzerland .
    [Show full text]
  • African Swine Fever T ∗ L.K
    Antiviral Research 165 (2019) 34–41 Contents lists available at ScienceDirect Antiviral Research journal homepage: www.elsevier.com/locate/antiviral African swine fever T ∗ L.K. Dixona, , H. Sunb, H. Robertsc a The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey, GU24 0NF, UK b Veterinary Faculty, Yangzhou University, Yangzhou, Jiangsu Province, PR China c Exotic Disease Control Team, Defra, Nobel House, 17 Smith Square, London, SW1P 3JR, UK ARTICLE INFO ABSTRACT Keywords: The continuing spread of African swine fever (ASF) outside Africa in Europe, the Russian Federation, China and African swine fever virus most recently to Mongolia and Vietnam, has heightened awareness of the threat posed by this devastating Epidemiology disease to the global pig industry and food security. In this review we summarise what we know about the Vaccines African swine fever virus (ASFV), the disease it causes, how it spreads and the current global situation. We Transmission discuss current control methods in domestic and wild pigs and prospects for development of vaccines and other tools for control. 1. Introduction 2. African swine fever virus Pigs provide an important source of high-quality protein and pro- ASF is caused by a large double-stranded DNA virus that replicates duction is predicted to increase in future to meet growing global de- in the cell cytoplasm and is the only member of the Asfarviridae family mands for meat. However, the supply of pork is threatened by infectious (Fig. 1). There are no closely related viruses (Alonso et al., 2018). The diseases, and amongst these African swine fever (ASF) is currently main target cells for ASFV replication are macrophages.
    [Show full text]
  • Structure–Function Analysis of Neutralizing Antibodies to H7N9 Influenza from Naturally Infected Humans
    ARTICLES https://doi.org/10.1038/s41564-018-0303-7 Structure–function analysis of neutralizing antibodies to H7N9 influenza from naturally infected humans Kuan-Ying A. Huang 1,2,17*, Pramila Rijal3,17, Haihai Jiang4,5,17, Beibei Wang6,7,8,17, Lisa Schimanski3, Tao Dong3,6, Yo-Min Liu9, Pengxiang Chang10, Munir Iqbal10, Mu-Chun Wang11, Zhihai Chen8,12, Rui Song8,12, Chung-Chi Huang13, Jeng-How Yang14, Jianxun Qi4, Tzou-Yien Lin1,2, Ang Li7,8, Timothy J. Powell 3, Jia-Tsrong Jan9, Che Ma9, George F. Gao 4,15,16*, Yi Shi 4,15,16* and Alain R. Townsend 3,6* Little is known about the specificities and neutralization breadth of the H7-reactive antibody repertoire induced by natural H7N9 infection in humans. We have isolated and characterized 73 H7-reactive monoclonal antibodies from peripheral B cells from four donors infected in 2013 and 2014. Of these, 45 antibodies were H7-specific, and 17 of these neutralized the virus, albeit with few somatic mutations in their variable domain sequences. An additional set of 28 antibodies, isolated from younger donors born after 1968, cross-reacted between H7 and H3 haemagglutinins in binding assays, and had accumulated signifi- cantly more somatic mutations, but were predominantly non-neutralizing in vitro. Crystal structures of three neutralizing and protective antibodies in complex with the H7 haemagglutinin revealed that they recognize overlapping residues surrounding the receptor-binding site of haemagglutinin. One of the antibodies, L4A-14, bound into the sialic acid binding site and made contacts with haemagglutinin residues that were conserved in the great majority of 2016–2017 H7N9 isolates.
    [Show full text]
  • The Pirbright Institute
    ~~ Companies House APOl(ef) Appointment of Director 111111111111111111 II X2ZMMHKW Company Name: THE PIRBRIGHT INSTITUTE Company Number: 00559784 Received for filing in Electronic Format on the: 15/01/2014 New Avvointment~ ..._ Details Date ofAppointment: 19/12/2013 Name: SIR BERTIE ROSS Consented to Act: YES Service Address: 33 ANHALT ROAD LONDON UNITED KINGDOM SW114NZ Country/State Usually Resident: UNITED KINGDOM Date ofBirth: 27/02/1950 Nationality: BRITISH Occupation: CONSULTANT Electronically Filed Document for Company Number: 00559784 Page: 1 Former Names: Authorisation Authenticated This form was authorised by one ofthe following: Director, Secretary, Person Authorised, Administrator, Administrative Receiver, Receiver, Receiver Manager, Charity Commission Receiver and Manager, CIC Manager, Judicial Factor. End ofElectronically Filed Document for Company Number: 00559784 Page: 2 THE PIRBRIGHT INSTITUTE (LIMITED BY GUARANTEE) TRUSTEES' REPORT AND FINANCIAL STATEMENTS FOR THE YEAR ENDED 31MARCH2014 · 11111111111111111111 . *A3LVTHIH* . A18 · 02/12/2014 #142 · COMPANIES HOUSE · Company registered number 559784 Charity registered number 228824 THE PIRBRIGHT INSTITUTE (LIMITED BY GUARANTEE) TRUSTEES' REPORT AND FINANCIAL STATEMENTS For the year ended 31 March 2014 Trustees: Professor Q McKellar CBE - Chair Mr R Butler Dr A Craig Dr T Kanellos MrTKeyMBE Mr RLouth Dr V Mayatt Sir B Ross Professor D Rowlands MrM Samuel Professor J Stephenson Director of the Institute: Professor J Fazakerley BSc, MBA, PhD, FSB, FRCPath Secretary: Mr R S
    [Show full text]